1. Technical Field of the Invention
The present invention relates to novel biaromatic compounds which are analogues of vitamin D.
The present invention also relates to the process for their preparation and their formulation into pharmaceutical compositions suited for applications in human or veterinary medicine, or, alternatively, formulated into cosmetic compositions.
The novel family of compounds according to the invention includes compounds which have a marked activity in the fields of cell differentiation and proliferation and find applications, more particularly, in the topical and systemic treatment of dermatological conditions (and the like) linked to a keratinization disorder, of conditions with an inflammatory and/or immunoallergic components and of hyperproliferation of tissues of ectodermal origin (skin, epithelium and the like), whether benign or malignant. These compounds may, in addition, be administered to combat skin aging, whether photoinduced or chronologic, and to treat cicatrization disorders.
It is also possible to use the compounds according to the invention in cosmetic compositions for body and hair hygiene.
2. Description of Background and/or Related and/or Prior Art
Vitamin D is an essential vitamin for the prevention and treatment of defects in the mineralization of cartilage (rickets), and of bone (osteomalacia), and even of certain forms of osteoporosis in the elderly subject. However, it is now accepted that its functions extend well beyond the regulation of bone metabolism and of calcium homeostasis. Among these, there may be mentioned its actions on cell proliferation and differentiation and the control of the immune defenses. Their discovery has paved the way for new therapeutic approaches in dermatology, cancerology as well as in the field of autoimmune diseases and that of organ and tissue transplants.
An effective therapeutic application has for long been hampered by the toxicity of this vitamin (hypercalcaemia which is sometimes fatal). Currently, structural analogues of vitamin D are synthesized, certain of which conserve only the differentiating properties and have no action on calcium metabolism.
WO 00/10958 describes vitamin D3-mimetic nonsecosteroidal biaromatic compounds, which are ligands for the VDR receptor. These compounds find applications in the treatment of pathologies linked to the deregulation of calcium metabolism. However, the general structure of these compounds is substantially different from that of the compounds of the present invention; indeed, the two aromatic rings of the compounds described in WO 00/10958 are linked to each other by a carbon atom whereas for the compounds of this invention, the two aromatic rings are linked by a chain comprising three atoms.
Likewise, WO 00/26167 and WO 01/38320 propose bicyclic compounds which are analogues of vitamin D and WO 01/38303 describes triaromatic compounds which are also analogues of vitamin D. These three classes of compounds exhibit, here again, chemical structures which are quite different from that of the compounds of the present invention.